Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer

Bojesen S.E.; Pooley K.A.; Johnatty S.E.; Brown Beesley Barwell Benitez J.; Matsuo Muir Michailidou K.; Tyrer J.P.; Edwards S.L.; Pickett H.A.; Shen H.C.; Smart C.E.; Hillman K.M.; Mai P.L.; Lawrenson K.; Stutz M.D.; Laitman Lu Y.; Karevan R.; Woods Wentzensen N.; Johnston R.L.; French J.D.; Chen X.; Weischer M.; Nielsen S.F.; Maranian M.J.; Gore Garcia-Closas Ghoussaini M.; Ahmed S.; Blomqvist Baynes C.; Bolla M.K.; Wang Q.; Dennis J.; McGuffog L.; Barrowdale D.; Lophatananon Lindblom Lee Leminen A.; Healey Hosono S.; Lush M.; Tessier D.C.; Van Den Berg Vincent D.; Bacot F.; Vergote I.; Lambrechts S.; Despierre Dicks E.; Risch H.A.; Gentry-Maharaj Gonzalez-Neira A.; Rookus Rossing M.A.; Pita G.; Doherty J.A.; Arnold Alvarez N.; Larson M.C.; Fridley B.L.; Siddiqui Schoof N.; Chang-Claude J.; Cicek M.S.; Paul Permuth-Wey Peto J.; Kalli K.R.; Broeks Borg Brooks-Wilson Berchuck A.; Armasu S.M.; Schmidt M.K.; Braaf L.M.; Winterhoff Wappenschmidt B.; Nevanlinna H.; Konecny G.E.; Lambrechts D.; Rodriguez-Rodriguez Rogmann L.; Guenel P.; Toloczko-Grabarek Teoman A.; Milne R.L.; Garcia J.J.; Cox A.; Shridhar V.; Buecher Burwinkel Bonanni Bressac-De Paillerets Brouwers B.; Marme F.; Hein R.; Sawyer E.J.; Haiman C.A.; Wang-Gohrke S.; Andrulis I.L.; Moysich K.B.; Hopper J.L.; Odunsi Offit K.; Lophatananon Lindblom Lee Leminen A.; Giles G.G.; Brenner Brauch H.; Simard J.; Lurie G.; Fasching P.A.; Carney M.E.; Radice P.; Wilkens L.R.; Schneeweiss Swerdlow A.; Goodman M.T.; Brenner Brauch H.; Gore Garcia-Closas Ghoussaini M.; Harter Hillemanns Hall P.; Winqvist R.; Durst Dumont M.; Devilee P.; Runnebaum I.; Jager Jukkola-Vuorinen Jakubowska Jensen A.; Long Lissowska Lubinski Lester Liu J.; Meindl Mannermaa A.; Brown Butzow R.; Bogdanova N.V.; Dork T.; Pelttari L.M.; Zheng W.; Lophatananon Lindblom Lee Leminen A.; Anton-Culver H.; Bunker C.H.; Kristensen Kataja V.; Ness R.B.; Matsuo Muir Michailidou K.; Edwards R.; Meindl Mannermaa A.; Heitz F.; Matsuo Muir Michailidou K.; Dansonka-Mieszkowska Du Bois A.; Wu A.H.; Harter Hillemanns Hall P.; Teo S.-H.; Schwaab I.; Shu X.-O.; Blot W.; Healey Hosono S.; Kang D.; Nakanishi T.; Hoatlin Hartman M.; Yatabe Y.; Hamann U.; Karlan B.Y.; Stewart-Brown Slager Sangrajrang S.; Kjaer S.K.; Gaborieau V.; Jager Jukkola-Vuorinen Jakubowska Jensen A.; Eccles D.; Hogdall E.; Shen C.-Y.; Brown Beesley Barwell Benitez J.; Woo Y.L.; Shrubsole Soller Shah M.; Azmi M.A.N.; Luben R.; Omar S.Z.; Czene K.; Vierkant R.A.; Nordestgaard Bo.G.; Flyger H.; Vachon C.; Olson J.E.; Wang X.; Levine D.A.; Rudolph A.; Weber R.P.; Frost Flesch-Janys D.; Iversen E.; Nickels S.; Schildkraut J.M.; Silva I.D.S.; Cramer D.W.; Gibson L.; Terry K.L.; Fletcher O.; Vitonis A.F.; Van Der Schoot C.E.; Poole E.M.; Hogervorst F.B.L.; Tworoger S.S.; Long Lissowska Lubinski Lester Liu J.; Bandera E.V.; Long Lissowska Lubinski Lester Liu J.; Olson S.H.; Humphreys K.; Orlow I.; Blomqvist Baynes C.; Rodriguez-Rodriguez Rogmann L.; Aittomaki K.; Salvesen H.B.; Muranen T.A.; Wauters Wik E.; Buecher Burwinkel Bonanni Bressac-De Paillerets Brouwers B.; Krakstad C.; Wauters Wik E.; Halle M.K.; Wildiers H.; Kiemeney L.A.; Mulot C.; Aben K.K.; Laurent-Puig Lichtner P.; Altena A.M.; Truong T.; Massuger L.F.A.G.; Brown Beesley Barwell Benitez J.; Pejovic T.; Perez J.I.A.; Hoatlin Hartman M.; Zamora M.P.; Cook L.S.; Balasubramanian S.P.; Kelemen L.E.; Schneeweiss Swerdlow A.; Le N.D.; Sohn Seynaeve Stegmaier Sutter Shapiro C.; Broeks Borg Brooks-Wilson Berchuck A.; Tomlinson I.; Kennedy Kerin M.J.; Miller N.; Cybulski C.; Henderson B.E.; Menkiszak McKay J.; Schumacher F.; Woods Wentzensen N.; Le Marchand L.; Yang H.P.; Mulligan A.M.; Glendon Giannini G.; Engelholm S.A.; Knight J.A.; Hogdall C.K.; Apicella C.; Gore Garcia-Closas Ghoussaini M.; Tsimiklis H.; Song H.; Southey M.C.; Jager Jukkola-Vuorinen Jakubowska Jensen A.; Den Ouweland A.M.W.; Brown Butzow R.; Martens J.W.M.; Flanagan J.M.; Kriege M.; Paul Permuth-Wey Peto J.; Manoukian Margolin Mazoyer S.; Siddiqui Schoof N.; Severi G.; Whittemore A.S.; Baglietto Bernard L.; McGuire V.; Sohn Seynaeve Stegmaier Sutter Shapiro C.; Sieh W.; Muller Miao Meijers-Heijboer H.; Arndt V.; Labreche F.; Gao Y.-T.; Goldberg M.S.; Yang G.; Durst Dumont M.; McLaughlin J.R.; Hartmann Hollestelle A.; Ekici A.B.; Beckmann M.W.; Phelan C.M.; Lux M.P.; Paul Permuth-Wey Peto J.; Peissel B.; Sellers T.A.; Ficarazzi F.; Barile Bidzinski M.; Ziogas A.; Ashworth A.; Gentry-Maharaj Gonzalez-Neira A.; Jones M.; Ramus S.J.; Orr N.; Menon U.; Pearce C.L.; Byrski Bruning T.; Pike M.C.; Ko Y.-D.; Long Lissowska Lubinski Lester Liu J.; Figueroa J.; Kupryjanczyk J.; Chanock S.J.; Dansonka-Mieszkowska Du Bois A.; Jager Jukkola-Vuorinen Jakubowska Jensen A.; Rzepecka I.K.; Pylkas K.; Barile Bidzinski M.; Kauppila S.; Hartmann Hollestelle A.; Sohn Seynaeve Stegmaier Sutter Shapiro C.; Tollenaar R.A.E.M.; Durda K.; Jaworska K.; Hartikainen J.M.; Kosma V.-M.; Kristensen Kataja V.; Antonenkova N.N.; Long Lissowska Lubinski Lester Liu J.; Shrubsole Soller Shah M.; Deming-Halverson S.; Lophatananon Lindblom Lee Leminen A.; Siriwanarangsan Soucy P.; Stewart-Brown Slager Sangrajrang S.; Ditsch N.; Laurent-Puig Lichtner P.; Schmutzler R.K.; Iwata Ito H.; Iwata Ito H.; Tajima K.; Tseng C.-C.; Stram D.O.; Van Den Berg Vincent D.; Yip C.H.; Ikram M.K.; Teh Y.-C.; Cai H.; Lu W.; Signorello L.B.; Cai Q.; Noh D.-Y.; Yoo K.-Y.; Muller Miao Meijers-Heijboer H.; Iau P.T.-C.; Teo Y.Y.; Menkiszak McKay J.; Sohn Seynaeve Stegmaier Sutter Shapiro C.; Ademuyiwa F.; Fountzilas G.; Hsiung C.-N.; Yu J.-C.; Hou M.-F.; Healey C.S.; Luccarini C.; Peock S.; Stoppa-Lyonnet D.; Peterlongo P.; Rebbeck T.R.; Piedmonte M.; Singer C.F.; Fineberg Friedman E.; Thomassen M.; Odunsi Offit K.; Hansen T.V.O.; Neuhausen S.L.; Szabo C.I.; Blanco I.; Garber Gronwald J.; Narod S.A.; Weitzel J.N.; Montagna M.; Olah E.; Godwin A.K.; Yannoukakos D.; Goldgar D.E.; Caldes Cole T.; Imyanitov E.N.; Tihomirova L.; Arun B.K.; Campbell I.; Mensenkamp A.R.; Van Asperen C.J.; Van Roozendaal K.E.P.; Muller Miao Meijers-Heijboer H.; Collee Cunningham J.M.; Oosterwijk J.C.; Hooning M.J.; Rookus Rossing M.A.; Van Der Luijt R.B.; Os T.A.M.; Evans D.G.; Frost Flesch-Janys D.; Fineberg Friedman E.; Brown Beesley Barwell Benitez J.; Walker L.; Kennedy Kerin M.J.; Platte R.; Davidson Dolcetti R.; Ellis S.D.; Caldes Cole T.; Buecher Burwinkel Bonanni Bressac-De Paillerets Brouwers B.; Buecher Burwinkel Bonanni Bressac-De Paillerets Brouwers B.; Damiola F.; Faivre Foretova L.; Frenay M.; Sinilnikova O.M.; Caron O.; Giraud S.; Manoukian Margolin Mazoyer S.; Bonadona V.; Caux-Moncoutier V.; Toloczko-Grabarek Teoman A.; Garber Gronwald J.; Byrski Bruning T.; Spurdle A.B.; Buecher Burwinkel Bonanni Bressac-De Paillerets Brouwers B.; Zaffaroni D.; Glendon Giannini G.; Baglietto Bernard L.; Davidson Dolcetti R.; Manoukian Margolin Mazoyer S.; Arnold Alvarez N.; Engel C.; Deissler H.; Rhiem K.; Niederacher D.; Plendl H.; Sohn Seynaeve Stegmaier Sutter Shapiro C.; Winterhoff Wappenschmidt B.; Broeks Borg Brooks-Wilson Berchuck A.; Melin B.; Rantala J.; Shrubsole Soller Shah M.; Nathanson K.L.; Domchek S.M.; Rodriguez G.C.; Salani R.; Kaulich D.G.; Tea M.-K.; Paluch S.S.; Laitman Lu Y.; Skytte A.-B.; Kruse T.A.; Jensen U.B.; Robson M.; Gerdes A.-M.; Ejlertsen B.; Faivre Foretova L.; Savage S.A.; Long Lissowska Lubinski Lester Liu J.; Siriwanarangsan Soucy P.; Kuchenbaecker K.B.; Olswold C.; Collee Cunningham J.M.; Stewart-Brown Slager Sangrajrang S.; Pankratz V.S.; Despierre Dicks E.; Lakhani S.R.; Couch F.J.; Harter Hillemanns Hall P.; Monteiro A.N.A.; Gayther S.A.; Pharoah P.D.P.; Reddel R.R.; Goode E.L.; Greene M.H.; Easton D.F.; Broeks Borg Brooks-Wilson Berchuck A.; Antoniou A.C.; Chenevix-Trench G.; Dunning A.M.

Journal Article

Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer

S.E. B
K.A. P
S.E. J
et al.

Nature Genetics (2013)

ISSN: 1061-4036

N/ACitations

5Readers

Abstract

TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ~480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 null 10 -7), lower risks for estrogen receptor (ER)-negative (P = 1.0 null 10 -8) and BRCA1 mutation carrier (P = 1.1 null 10 -5) breast cancers and altered promoter assay signal. The minor allele at the peak 2 SNP rs7705526 associates with longer telomeres (P = 2.3 null 10 -14), higher risk of low-malignant-potential ovarian cancer (P = 1.3 null 10 -15) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 null 10 -12) and BRCA1 mutation carrier (P = 1.6 null 10 -14) breast and invasive ovarian (P = 1.3 null 10 -11) cancer risks but not via altered telomere length. The cancer risk alleles of rs2242652 and rs10069690, respectively, increase silencing and generate a truncated TERT splice variant.

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S.E., B., K.A., P., S.E., J., J., B. B. B. B., K., M. M. M., J.P., T., … A.M., D. (2013). Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Nature Genetics.

Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer

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